Dr. Rogers: Hi, I'm Dr. Kerry Rogers. I'm a hematologist at the Ohio State University, and I specialize in taking care of people with chronic lymphocytic leukemia and hairy cell leukemia. I'm here at the American Society of Clinical Oncology Annual Meeting in 2023, and excited to see all the great science going on with CLL.
Graphic: Should patients treated with IBR, a once-daily Bruton's tyrosine inhibitor, have flexibility in their dosing?
Dr. Rogers: The study that was done looking at changing the dose of ibrutinib (Imbruvica) and how that went for patients is a really important one. So this is one that I did in collaboration with Janssen Real World Oncology. So it was using data generated from what we call real-world evidence, which is data from patients actually taking the drug not as the participants in a clinical trial. So as most people know, how we understand how drugs work for people to treat CLL is usually from clinical trials where people were given the drug as a participant in a research study. However, once drugs are approved, there's the opportunity to look at the real experience of people taking the drug.
So this study looked at almost 1,200 people who took ibrutinib to treat CLL, and it wasn't people that were participating in a research study. There are people who took it either at participating community or academic sites, where data was obtained from medical records to see how their experience was. And the major question we had was, if you need to reduce the dose of ibrutinib for a side effect or something like that, does this change how well the ibrutinib works to treat CLL? And this is a question people ask me all the time when we're talking about reducing the dose to help something like muscle aches, or some side effect that's not life-threatening, but it's clearly impairing someone's quality of life to them. What will that do if I reduce the dose of ibrutinib? Is this going to change how it helps my CLL is a question I get asked a lot.
So within this study, which again, had almost 1,200 people that were included, it was trying to capture people taking ibrutinib as a first treatment, although there are some limitations to looking at this kind of data. And we saw that 19.6% of people, which is almost one out of five people, did have a dose reduction in the ibrutinib dose. We think that most of this was for side effects, but we don't know for sure, because again, this is looking at a real-world experience.
The really cool part is that we saw that the time to starting the next treatment after ibrutinib was not different between the people that got a dose reduction, that 19.6% that got a dose reduction of ibrutinib, and those that didn't. So really, if people are staying on the drug and not needing the next treatment for CLL sooner, it suggests that the effectiveness of the ibrutinib is still there, even though the dose has been reduced.
We also did something in this that was really neat, which is looking at something we call adherence. Which is how well people are actually getting and taking the medication at home, or if there's any reason that people aren't able to take their medication once a day as prescribed. And those are looking at, did people refill their prescriptions, for the most part. Because if people aren't taking the drug, they don't get their prescription refilled as well. And it actually saw that the percentage of people who were refilling prescriptions and engaged in taking the drug regularly was actually slightly more in the group that had a dose reduction or had to have the dose of the ibrutinib reduced. So to me, that really tells me that reducing the dose helped those people be able to stay on ibrutinib and take it as their physician had prescribed it.
So I think the overall summary of this is that it was a study, in collaboration with myself and Janssen real-world evidence, to capture the experience of almost 1,200 people living with CLL who were taking ibrutinib. And we found, almost one out of five patients had a reduction in their ibrutinib dose, and that those that had their dose reduced, had the same time to – before they needed the next treatment, as those who didn't have their dose reduced. This to me means that you can expect the disease outcome, or the benefit you get for your CLL from ibrutinib to be the same, even if you've had to have the dose reduced. And we found that people's ability to take the medication was actually better. So taking it regularly or being adherent to the medication was better if they had their dose reduced, likely meaning that the side effects were better.
Graphic: Has there been anything presented at ASCO 2033 about CLL and COVID-19?
Dr. Rogers: I really am excited about a study we did at our institution looking at this. So, as we all know, we've seen improvements in the experience of people who get COVID-19, where it's not really as devastating in terms of hospital stays, or people dying from COVID in recent times as it was in the past. We also know that when vaccines came out that the amount of antibody responses we were seeing in people living with CLL after they got a COVID vaccine, was less than in healthy adults that didn't have CLL. And at our institution, we see a lot of people living with CLL, and we wanted to look at the experience to see if getting COVID vaccines reduced people's risk of getting COVID if they had CLL.
And then also, the outcomes of people that got COVID-19 after they've received vaccination.
So the data we found was very similar to what other people saw, which is that rates of antibody responses to the vaccine, in people living with CLL, were less than you'd expect in healthy adults. And that certain treatments, like anti-CD20 monoclonal antibodies, reduced the rate of getting an antibody response to the vaccine. However, we did have 80 people that got COVID-19 after receiving the vaccine, and only five of those people died after that time, four of them from COVID-19, and one from something unrelated. So that's about 12% of people getting COVID-19 after the vaccine, dying of COVID, compared to the 30 to 33% we were seeing in the early experience.
So for anyone that doesn't know this, looking both at the time and back at the data from the beginning of the COVID-19 pandemic, most studies are showing between 30 and 33% of people living with CLL who got COVID died of it. And now, at least in our own experience at our institution, after the vaccine, that number is less. And we actually expect that to further go down, as we see better outcomes across all populations with COVID-19 infection.
Graphic: How do different ethnic and racial populations experience CLL?
Dr. Rogers: To start with, I just want to say, when you look at the demographics of who is living with CLL, about nine out of 10 people living with CLL are white. So the number of people from different racial or ethnic backgrounds living with CLL is less than the number of people who are white living with CLL. And that actually has to do with the genetics and the biology of who actually gets CLL. However, we've definitely realized, as a field, that who's in clinical trials is actually more white people than you would expect. And that we're probably not necessarily representing some of the racial or ethnic minority populations who have CLL in our large clinical trials. And there are many reasons for that, and that's something that's not specific to CLL but is seen across many diseases in oncology.
So each disease has its own biology of who actually ends up developing the disease. There are more Black people that get multiple myeloma. But you have to be mindful, as both a physician and as an investigator or someone doing research in a disease, that you want to make sure you understand the disease experience for the whole group of people living with it, just not people who are white, even though that's the majority.
There has been a lot of research effort to try to understand if there are differences in disease biology or the disease, like risk features or characteristics of people with different skin colors, racial, or ethnic backgrounds that develop CLL. And then also, if their outcomes are how long they can expect to live with CLL, how well or how much they benefit from treatment is different.
There was some very interesting research presented at this meeting, at least two different studies, looking at outcomes for people with CLL that are participants in clinical trials or are seen at a center where they specialize in a lot of CLL and have participated in a registry. So it's physicians, even if they're not at a large CLL program like we have at Ohio State, are engaged in the CLL community.
And it actually looks like the experience of Black individuals living with CLL, in terms of disease outcomes, is similar to that of white people living with CLL if you look at progression-free survival of something like ibrutinib.
And again, these are people seen at hospitals where the physicians are interested in CLL and have opened up at least one registry study to try to learn more about CLL. That's actually not what is seen in something like a database. My colleague is doing a study looking at the Flatiron database, and you actually see that Black people living with CLL don't do as well. And that might be because of different access to treatments, or maybe less able to see a CLL expert or be seen at a center where they treat a lot of CLL.
And we all know there are many factors that go into whether or not you can see a CLL expert, such as financial ability, travel time, and an interest in doing that. Learning about how important it is to see a CLL expert, especially if things aren't going great with your CLL. And so, because of this, we actually think that access to expert care, these differences across studies, where people were seen at centers with an interest are not necessarily, so I feel that might play a role.
And then I think there's going to be continued effort and enthusiasm in the field to learn more about differences in disease biology, or how we might improve access to care for different groups of CLL patients. And just because Black individuals with CLL might not be in the majority of people experiencing CLL, it doesn't mean that we should ignore their experience. It's still very important. When you look at individuals of Hispanic background, or Asian individuals, that's an even smaller group when you look at the biology of who has CLL. So I think it would be important to continue to look at those groups of people too, just so we can make sure that we take care of everybody living with CLL in the best possible way.
Graphic: What other top highlights do you want to share with CLL patients and care partners?
Dr. Rogers: My colleague, Dr. Jennifer Woyach, at the Ohio State University, is presenting some initial results from an ALLIANCE trial. So for anyone that's not familiar with the ALLIANCE, it's a U.S. oncology cooperative group. So that's a group of hospitals that get together to do clinical trials and research in cancers, and this was a study in CLL in older individuals. So, initially, 75 and up, although they did amend it to allow 65 and up, that's comparing two different treatments for CLL. So it's comparing a treatment of ibrutinib and obinutuzumab (Gazyva) to a treatment of ibrutinib, venetoclax (Venclexta), and obinutuzumab, which is given mostly for a defined duration. Although some people did continue ibrutinib if they still had detectable CLL at the end of treatment.
And I think there are a couple of take-home points from that. One is that the effectiveness of both arms of treatment in the study was outstanding. So people in this study did very well with their CLL treatment, and these are people taking their very first treatment for CLL. So that, to me, was really nice to see. The study was actually designed to see if the three-drug regimen, that's given in many cases for just a fixed time period, was going to be better, in terms of progression-free survival, which is how long people are alive without their CLL coming back. And it looks like, actually, the three-drug regimen is not better or superior. It actually looks very similar. So that means that the study didn't meet its goal of proving that the three-drug regimen was better. But for me, as someone taking care of people with CLL, knowing that this isn't worse, and is a defined time period regimen, is actually a very important thing.
The other thing that was very interesting about this particular study is, it looks like the impact of COVID-19 might have been quite substantial. And in fact, if you look at both of the arms and if you remove people that died of COVID-19, both treatments actually look much similar. And it looks like we might have some people that – more people died of COVID-19 in the three-drug regimen, and three drugs is more immunosuppressive. So I don't know if that's something moving forward that's a high concern, especially when we're seeing outcomes with COVID-19 infection are better for our CLL patients than they were obviously in 2020 and 2021. But it is interesting to see that removing deaths from COVID-19 does make a difference between these two different treatments, in how people are doing, as to why that was seen, will be an ongoing subject of study.
So I guess, overall for that, I'm grateful that so many people chose to participate in such a nice, large study. This is how we answer important questions in the field that allow us to give our patients answers for what we expect for them when they undergo treatment. I think that for everyone that participated in the study – there's actually a similar study in younger patients that are done through ECOG – participating in this study likely benefited them, as well as benefiting knowledge. And while it's disappointing to see that the three drugs weren't necessarily better because that's what we were testing, it is nice to see those outcomes were at least similar, and I look forward to seeing more of the analysis from that trial. But the preliminary results were presented at this meeting, and I think that's really an important thing that's going to be useful for understanding how we need to treat people living with CLL.
